By Philip R. Fischer, MD, DTM&H
Professor of Pediatrics, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN; Department of Pediatrics, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates
SYNOPSIS: Pregnant women can develop malaria in non-endemic areas, even when they are far removed from malaria exposure both geographically and temporally.
SOURCE: Guida Marascia F, Colomba C, Abbott M, et al. Imported malaria in pregnancy in Europe: A systematic review of the literature of the last 25 years. Travel Med Infect Dis 2023; Nov 24:102673. doi: 10.1016/j.tmaid.2023.102673. [Online ahead of print].
During pregnancy, malaria is associated with severe maternal illness and adverse pregnancy outcomes. Asymptomatic women infected with Plasmodium who travel, such as the many women traveling or migrating from Africa to Europe, subsequently can become ill with pregnancy-related malaria. With only limited literature about imported malaria of pregnant women in Europe, Guida Marascia and colleagues reported a case of malaria in a pregnant woman in Europe and then reviewed published literature on the topic.
The authors saw a 22-year-old Nigerian woman in Italy who had not been in a malaria-endemic area for more than five years who presented with abdominal pain during her 23rd week of pregnancy. She was afebrile, with a physical exam notable only for pregnancy but with ultrasound evidence of hepatosplenomegaly (18.5 cm long spleen). Her hemoglobin concentration was low at 5 gm/dL. There was no evidence of bleeding or autoimmune disease. Despite very low suspicion of malaria, tests were positive for P. falciparum. The patient was treated with oral dihydroartemisinin-piperaquine, and parasitemia resolved. She continued to do well and had an uneventful delivery of a healthy baby, who was still well at 6 months of age.
Their interesting experience with this patient prompted the authors to review all PubMed-indexed papers related to imported malaria during pregnancy in Europe from 1997 through mid-2023. They identified 57 patients, in addition to their patient, diagnosed with malaria during pregnancy in Europe. Of the total 58 patients reviewed, more had been visiting friends and relatives in a malarial area than had recently immigrated to Europe for the first time. The median time away from a malarial area prior to diagnosis was 180 days (range 15 to 730). Of the women, 97% had been in Africa. On testing, 81% had P. falciparum, 10% had P. vivax, and the others had P. ovale or P. malariae. Overall, 17% of the women were asymptomatic, 48% were febrile at presentation, and 87% of those for whom blood counts were reported were anemic.
Pregnancy outcomes were favorable (healthy term baby of appropriate weight) for 59% of women; 7% of pregnancies ended with miscarriage; 12% of babies were born at low birthweight; and 17% of babies became ill with congenital malaria.
The authors rightly noted that women who developed anti-malaria immunity earlier in life have waning immunity against malaria during pregnancy. (This is related to helper T cell alterations in the Th1-Th2 immune balance during pregnancy.) They also explained that even asymptomatic women can harbor malaria parasites that sequester in their placentas.
COMMENTARY
Last month, Infectious Disease Alert reviewed new, simple treatment decision-making for malaria during pregnancy. Of course, a key to good treatment is accurate diagnosis. This review of imported malaria during pregnancy in Europe reminds us that the diagnosis of malaria during pregnancy is not always made in a timely fashion. As our patients return from global travels this post-holiday month, we need to be cognizant of the possibility of gestational malaria.
Guida Marascia only reviewed published case reports and series of malaria in pregnant women in Europe, finding 57 reported cases over 25 years (2.3 per year), to which they added their own. Clearly, the incidence of imported malaria is higher than that identified only in published articles. In the United States, where malaria cases are reported to the Centers for Disease Control and Prevention (CDC), there were 19 cases of malaria in pregnancy in 2018 (as reported in 2022); none of the 11 U.S. residents in that report had taken appropriate malaria chemoprophylaxis during their travel to malarial areas.1 Travelers to malarial areas, even those with some previous immunity who are traveling during pregnancy, should implement insect bite avoidance measures and should take preventive malaria medication.
In the CDC report, about two-thirds of the malaria was due to P. falciparum, and most malaria became symptomatic within 90 days of leaving the endemic area.1 Typically, P. falciparum becomes symptomatic within weeks of exposure, although later presentations (especially with subclinical smoldering infection that might become symptomatic with pregnancy or medical conditions altering underlying host immunity) have been noted.2,3 It is a bit surprising that Guida Marascia’s study, in which only 10% of patients had P. vivax malaria (which can become symptomatic long after initial infection when hypnozoites in the liver “wake up”), there were so many patients with prolonged gaps (most greater than six months) between exposure and the onset of symptoms. Even a remote history of travel to a malaria-endemic area should elevate concern for possible malaria in pregnant women.
Despite Guida Marascia’s set of patients being subject to bias whereby more unusual or complicated cases possibly would be more likely to be reported, there are several key lessons that affect clinical practice. First, travel histories are important when seeing febrile pregnant women, especially those with anemia. Second, P. vivax malaria is not necessarily benign; severe disease due to P. vivax has been increasingly reported in children, pregnant women, and other adults.4-6 Third, treating the mother is doubly important, since there is risk of both maternal and newborn consequences, including congenital malaria as seen in 17% of the newborns birthed by the women included in this European study.
REFERENCES
- Mace KE, Lucchi NW, Tan KR. Malaria Surveillance - United States, 2018. MMWR Surveill Summ 2022;71:1-35.
- Gallet S, Dard C, Bailly S, et al. Length of stay in at-risk areas and time to malaria attack on return. Infect Dis Now 2023;54:104819.
- Valle A, Yu NC, Giannakakos V, et al. A case of latent Plasmodium falciparum malaria in a patient with coexisting systemic lupus erythematosus (SLE) and neuromyelitis optica spectrum disorder (NMOSD). Cureus 2022;14:e30436.
- Arya A, Meena SS, Matlani M, et al. Trends in clinical features and severity of Plasmodium vivax malaria among children at tertiary care center in North India. J Trop Pediatr 2023;69:fmad034.
- Kojom Foko LP, Singh V. Malaria in pregnancy in India: A 50-year bird’s eye. Front Public Health 2023;11:1150466.
- López AR, Martins EB, de Pina-Costa A, et al. A fatal respiratory complication of malaria caused by Plasmodium vivax. Malar J 2023;22:303.
